Hollow tubular structures with specific internal diameters have attracted a great deal of attention lately due to their potential utility in inclusion chemistry, molecular transport, catalysis, and molecular electronics. Recently, we have developed an approach for the design of a new class of tubular structures termed "organic nanotubes". These structures which are constructed through self-assembly of ring-shaped cyclic peptide subunits have provided the first simple and practical approach for the design of open-ended hollow tubular structures with predetermined internal diameters and tailored surface properties. Here, we propose to study the application of such molecule building strategy toward biologically relevant processes in molecular inclusion and transport chemistry. Our goal is to develop strategies for the binding and facilitated transport of sugar substrates across lipid bilayers. Toward that end, we propose to design two classes of tubular systems. The first tubular system is a short cylindrical object designed for the solution- phase operations and provides a simple approach for the study of inclusion chemistry of simple sugars in both organic and aqueous solutions. The second system is based on nngshaped peptide structures which spontaneously partition into, and assemble, in the lipid bilayers to form cylindrical channel and pore structures. The synthetic strategy allows for the first time to study pore-mediated "molecular" transport across lipid bilayers. Furthermore, the ability to rationally form channel and pore structures in lipid bilayers is expected to exert cytotoxic effects in living cells. We therefore aim to study the cytotoxic and biological activity profiles of these compounds against a variety of cell lines. It is our hope that the research proposed here will bring us closer to achieving our long term goal aimed at the design of novel drug delivery vehicles and the design of a new class of selective and potent cytotoxic agents. The specific aims of the proposed research are: 1. Design, synthesis, and characterization of cyclic peptides for solution-phase self-assembly into cylindrical structures and the study of a) the effects of ring size, side chain identity, and covalent bond constraints on the assembly and stability of the peptide ensemble, and b) molecular inclusion properties and binding selectivity of sugars, nucleosides, and nucleotides within the internal hydrophilic cylindrical cavity of the designed cylindrical ensembles. 2. Study the scope and selectivity of self-assembled membrane channel structures in the pore-mediated transport of sugar substrates across lipid bilayers. 3. In vitro evaluation of the cytotoxicity profiles of channel and pore forming peptide structures, selected through a combinatorial peptide library approach, against a variety of bacterial strains and normal and malignant human and animal cell lines.